CN110018302A - It is a kind of new to cause pulmonary inflammatory diagnosing and treating reagent by liver diseases - Google Patents
It is a kind of new to cause pulmonary inflammatory diagnosing and treating reagent by liver diseases Download PDFInfo
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
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Abstract
The invention discloses a kind of new to cause pulmonary inflammatory diagnosing and treating reagent by liver diseases.MiR-122 is used as the pulmonary inflammatory biomarker as caused by liver diseases in blood.The reagent of miR-122 is preparing the application caused in pulmonary inflammatory diagnostic reagent by liver diseases in quantitative detection blood.MiR-122 in blood is preparing the application caused in pulmonary inflammatory drug by liver diseases as therapeutic targets.The magnetic bead being made up of antisense nucleic acid/glue bead is adsorbed to remove the miR-122 in blood, to reach treatment lung inflammation as caused by liver diseases.The present invention provides a kind of new theoretical explanation for the lung inflammation of the unknown cause as caused by liver diseases, and develops a kind of new diagnosing and treating reagent.
Description
Technical field
The invention belongs to biomedicine technical field, be related to it is a kind of it is new by liver diseases cause pulmonary inflammatory diagnosis and
Therapeutic reagent.
Background technique
Liver plays an important role in regulating system sexual organ inflammation.The liver of illness, which may generate multiple organ system, to be permitted
More adverse effects, including pulmonary system.Clinically, the pulmonary abnormalities of patients with chronic liver and symptom are common, and about three
Slight hypoxia is observed in/mono- patients with chronic liver.In fact, up to 70% cirrhosis for receiving liver transfer operation assessment
Patient complains expiratory dyspnea.Hepatopulmonary syndrome is characterized in intrapulmonary blood vessel dilatation, and gas exchanges are abnormal, and pulmonary edema and breathing are short
Promote, the major complications after hepatic ischemia/reperfusion injury and Reperfu- sion (I/R) damage after being hepatectomy or transplanting.It is reported that many factors, example
Such as systemic inflammatory reaction, it is related to Acute pulmonary inflammation caused by hepatic injury and tissue damage.Woods et al. observes that hepatic injury is logical
Increase lung iNOS induced expression injury of lungs is crossed, prompts iNOS expression that may play key effect in this phenomenon.In addition, a large amount of
Cysteinyl leukotriene (CysLTs), including LTB4, LTC4, LTD4 and LTE4 generate after being shown in hepatic injury and in pulmonary edema
It plays a significant role in development.Al-Amran et al. also indicates that LTs promotes acute lung injury caused by hemorrhagic shock.However,
Although being had made great progress in terms of illustrating the regulating networks of mediator and organ interaction of induction acute lung injury,
But the molecular basis that hepatic injury is connected with Acute pulmonary inflammation and tissue damage is not understood completely yet.
Microrna (miRNA) is the non-coding RNA that a kind of length is about 22 nucleotide, establishes object mistake of making a living by new
Gene regulator in journey.We and other people studies have shown that miRNA by microvesicle (MV) or protein mediated approach by
Various types of cell secretions.Biological characteristis and functional study further demonstrate that extracellular miRNA is highly stable, not only may be used
As the biomarker of various diseases, it is alternatively arranged as mediating the novel signal point of telecommunication between various cell types and organ
Son.Specifically, the circulation miRNA in MV may be delivered into recipient cell, wherein it is more to adjust to serve as interior miRNAs for they
A target gene or signal transduction event.For example, et al..Report miR-150 is selectively packaged into MV and thin in people's blood
It is actively secreted in the THP-1 cell of born of the same parents and culture.MV derived from THP-1 can enter and to deliver miR-150 thin to people HMEC-1
Born of the same parents, and raised external source miR-150 is effectively reduced c-Myb and expresses and enhance the migration in HMEC-1 cell.On the other hand,
The certain miRNA secreted in blood plasma also can't detect in MV, but related with rna binding protein, such as Argonaute 2 (AGO2)
With nucleophosmin 1 (NPM1).It is needed further however, illustrating effect of no MV circulation miRNA in cell-cell communication
Concern.
Translational repression is carried out except through the base pairing paratope point on said target mrna or direct mRNA degradation, miRNA exist
Conventional effect in posttranscriptional gene adjusting is outer, and miRNA can also be directly as the physiologic ligand of certain RNA receptors.So far
In the Toll-like receptor (TLR) of identification, the intracellular TLR7 of mouse and the TLR8 of the mankind can report identification external source rich in GU
Single stranded RNA (ssRNA) molecule, for example originating from the RN40 (HIV-1) of human immunodeficiency virus -1.It has recently been demonstrated that tool
There is the mature miRNA of the sequence rich in GU to promote immunostimulation also by as the physiologic ligand of mouse TLR7 and people TLR8.Example
Such as, miR-21, miR-29a, miR-25-3p and miR-92a-3p contain the sequence rich in GU, have been displayed and mouse TLR7 and people
TLR8 interacts with the secretion of proinflammatory cytokine in activating macrophage.It is consistent with this, Lehmann et al..It was found that another
A kind of miRNA, let-7b rich in GU, as effective activator of TLR7 signal transduction in neuron, inducing neural denaturation.So
And although the miRNA as R-848 shows that they are anti-by directly activation TLR signal transduction path initiation body inflammation
It answers, but it is still not that whether this unconventional effect works in the Acute pulmonary inflammation of hepatic injury induction and tissue damage
Know.
Summary of the invention
The purpose of the present invention is 1) provide a kind of lung inflammation that unknown cause is detected by miR-122 in detection blood
Whether applied as caused by liver diseases；2) provide one kind is caused to treat by liver diseases by miR-122 in absorption blood
Pulmonary inflammatory application.
The purpose of the present invention can be achieved through the following technical solutions:
In blood miR-122 (> hsa-miR-122-5p MIMAT0000421UGGAGUGUGACAAUGGUGUUUG,
(SEQ ID NO.1)) as detection target cause by liver diseases the application in pulmonary inflammatory diagnostic reagent in preparation.
The reagent of miR-122 is caused in pulmonary inflammatory diagnostic reagent in preparation by liver diseases in quantitative detection blood
Using.
The reagent of miR-122 preferably detects qRT-PCR primer and/or the spy of miR-122 in the quantitative detection blood
Needle.
One kind causing pulmonary inflammatory diagnostic reagent by liver diseases, the reagent comprising miR-122 in quantitative detection blood.
The diagnostic reagent preferably comprises the qRT-PCR primer and/or probe of detection miR-122.
MiR-122 in blood is caused answering in pulmonary inflammatory drug by liver diseases in preparation as therapeutic targets
With.
The magnetic bead being made up of antisense nucleic acid/glue bead is adsorbed to remove the miR-122 in blood, to reach treatment by liver
Lung inflammation caused by dirty disease.
It miR-122 or reduces the reagent of miR-122 expression quantity in blood in removal blood and is caused in preparation by liver diseases
Application in pulmonary inflammatory drug.
Magnetic bead/glue bead of the reagent preferably antisense nucleic acid containing miR-122 of miR-122 in the removal blood.
A kind of treat causes pulmonary inflammatory drug by liver diseases, it is characterised in that includes miR-122 in removal blood
Or reduce the reagent of miR-122 expression quantity in blood；It is preferred that magnetic bead/glue bead of the antisense nucleic acid containing miR-122.
MiR-122 in blood is screening the application caused in pulmonary inflammatory drug by liver diseases.
The preferred serum of heretofore described blood, blood plasma or whole blood.
The utility model has the advantages that
The lung inflammation of unknown cause is a major class of pneumonia, and according to patient symptom, sign and laboratory are checked, image
It learns and checks and can clarify a diagnosis as pneumonia, but can not find pathogenic factor.Present invention demonstrates that the lung of a big chunk unknown cause
Inflammation may be due to caused by liver diseases.We provide first evidences to show that the miR-122 of wounded hepatocytes release is
The arch-criminal of Acute pulmonary inflammation caused by hepatic injury and lung injury.Under the conditions of various hepatic injuries, blood plasma miR-122
Horizontal significant increase, and eliminate the miR-122 in mouse peripheral blood and consumingly weaken the Acute Lung inflammation induced by hepatic injury
Disease and lung injury.Labeled in situ and flow cytometry show that the circulation miR-122 of impaired mouse liver cell release is delivered
To lung tissue, especially pulmonary alveolar macrophage.In macrophage, miR-122 activates TLR7 signal transduction, leads to macrophage
The secretion of M1 polarization and inflammatory cytokine such as TNF α and IL-6.Support the specific phase interaction between miR-122 and mouse TLR7
With, miR-122 to the activation of mouse alveolar macrophages largely by TLR7 in depleted mice macrophage or
Mutation miR-122 in TLR7 binding sequence and be revoked.Based on the above principles, we have developed be based on quantitative PCR (qRT-
PCR real-time quantitative PCR diagnostic reagent) is used to detect miR-122 in the lung inflammation blood samples of patients of unknown cause, with miR-
122 contents judge whether the lung inflammation of unknown cause is caused by liver diseases.In addition, we also developed a kind of combination
The magnetic bead of miR-122 translation sequences/glue bead absorption is drawn to reach treatment by liver diseases with removing the miR-122 in blood
The lung inflammation risen.The present invention provides a kind of new Theory Solution for the lung inflammation of the unknown cause as caused by liver diseases
It releases, and develops a kind of new diagnostic and therapeutic method.
Detailed description of the invention
Fig. 1 present invention discover that liver release miR-122 induce pulmonary inflammatory pathogenesis
Fig. 2 quantitative PCR detection miR-122 content in the lung inflammation blood samples of patients due to caused by liver diseases
Fig. 3 quantitative PCR detection miR- in the lung inflammation blood samples of patients due to caused by liver diseases in mouse model
122 contents
All there is lung inflammation in the lung of mouse in Fig. 4 difference liver diseases model
By absorption miR-122 in Fig. 5 mouse model, mitigate the lung inflammation due to caused by liver diseases
Specific embodiment
Embodiment 1
It collects and suffers from lung inflammation, and liver also has the patient of disease, blood is detected by quantitative PCR (qRT-PCR)
Middle miR-122 content.Experimental result is as shown in Fig. 2, miR-122 content in the lung inflammation blood samples of patients as caused by liver diseases
It significantly rises.
Embodiment 2
We construct conA, and the various liver diseases models such as DEN and liver cancer are examined by quantitative PCR (qRT-PCR) first
The content of miR-122 in these liver diseases models is surveyed, next observes pulmonary inflammatory in these liver diseases mouse models
State.Experimental result shows that miR-122 significantly rises (Fig. 3) in the mouse model blood of liver diseases, and suffers from liver
All there is different degrees of inflammation (Fig. 4) in the mouse lung of disease.
Embodiment 3
The magnetic bead that we are constituted using miR-122 antisense nucleic acid/glue bead adsorbs the lung inflammation as caused by liver diseases
MiR-122 in mouse blood, observation remove in blood after miR-122, and mouse lung inflammation improves situation.Experimental result such as Fig. 5
It is shown, the lung inflammation due to caused by liver diseases in mouse, after we remove the miR-122 in blood, mouse lung
The inflammatory conditions in portion are greatly improved.
Sequence table
<110>Nanjing University
What<120>one kind was new causes pulmonary inflammatory diagnosing and treating reagent by liver diseases
<160> 1
<170> SIPOSequenceListing 1.0
<210> 1
<211> 22
<212> RNA
<213>mankind (homines)
<400> 1
uggaguguga caaugguguu ug 22
Claims (10)
1. the miR-122 in blood is caused answering in pulmonary inflammatory diagnostic reagent by liver diseases in preparation as detection target
With.
2. the reagent of miR-122 is caused answering in pulmonary inflammatory diagnostic reagent by liver diseases in preparation in quantitative detection blood
With.
3. application according to claim 3, it is characterised in that the reagent of miR-122 is inspection in the quantitative detection blood
Survey the qRT-PCR primer and/or probe of miR-122.
4. one kind causes pulmonary inflammatory diagnostic reagent by liver diseases, it is characterised in that include miR- in quantitative detection blood
122 reagent.
5. diagnostic reagent according to claim 4, it is characterised in that comprising detect miR-122 qRT-PCR primer and/or
Probe.
6. the miR-122 in blood is preparing the application caused in pulmonary inflammatory drug by liver diseases as therapeutic targets.
7. miR-122 or reducing the reagent of miR-122 expression quantity in blood in removal blood and by liver diseases causing lung in preparation
Application in the drug of portion's inflammation.
8. application according to claim 7, it is characterised in that the reagent of miR-122 is containing miR- in the removal blood
Magnetic bead/glue bead of 122 antisense nucleic acid.
9. a kind for the treatment of by liver diseases causes pulmonary inflammatory drug, it is characterised in that comprising miR-122 in removal blood or
Reduce the reagent of miR-122 expression quantity in blood；It is preferred that magnetic bead/glue bead of the antisense nucleic acid containing miR-122.
10. the miR-122 in blood is screening the application caused in pulmonary inflammatory drug by liver diseases.
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110724740A (en) * | 2019-11-27 | 2020-01-24 | 中国人民解放军陆军军医大学第一附属医院 | Long-chain non-coding RNA for screening hepatopulmonary syndrome and application thereof |
| CN113632765A (en) * | 2021-03-31 | 2021-11-12 | 中山大学中山眼科中心 | Retina neovascular disease animal model, construction method and application thereof |
| CN115337322A (en) * | 2021-05-13 | 2022-11-15 | 南京大学 | Application of RNA in preparation of product for treating pulmonary fibrosis related diseases |
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| US20020001825A1 (en) * | 2000-03-31 | 2002-01-03 | Nobuyuki Itoh | Fibroblast growth factor-like molecules and uses thereof |
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| CN113632765B (en) * | 2021-03-31 | 2023-01-03 | 中山大学中山眼科中心 | Retina neovascular disease animal model, construction method and application thereof |
| CN115337322A (en) * | 2021-05-13 | 2022-11-15 | 南京大学 | Application of RNA in preparation of product for treating pulmonary fibrosis related diseases |
| CN115337322B (en) * | 2021-05-13 | 2024-04-19 | 南京大学 | Application of RNA in preparation of products for treating pulmonary fibrosis related diseases |
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